1. Field of the Invention
The present invention relates generally to methods and apparatus for the pulmonary delivery of drugs. More particularly, the present invention relates to a method and apparatus for dispersing dry powder medicaments for inhalation by a patient.
Effective delivery to a patient is a critical aspect of any successful drug therapy. Various routes of delivery exist, and each has its own advantages and disadvantages. Oral drug delivery of pills, capsules, elixirs, and the like, is perhaps the most convenient method, but many drugs are degraded in the digestive tract before they can be absorbed. Such degradation is a particular problem with modern protein drugs which are rapidly degraded by proteolytic enzymes in the digestive tract. Subcutaneous injection is frequently an effective route for systemic drug delivery, including the delivery of proteins, but enjoys a low patient acceptance. Since injection of drugs, such as insulin, one or more times a day can frequently be a source of poor patient compliance, a variety of alternative routes of administration have also been developed, including transdermal, intranasal, intrarectal, intravaginal, and pulmonary delivery.
Of particular interest to the present invention, pulmonary drug delivery relies on inhalation of a drug dispersion or aerosol by the patient so that active drug within the dispersion can reach the distal (alveolar) regions of the lung. It has been found that certain drugs are readily absorbed through the alveolar region directly into blood circulation. Pulmonary delivery is particularly promising for the delivery of proteins and polypeptides which are difficult to deliver by other routes of administration. Such pulmonary delivery is effective both for systemic delivery and for localized delivery to treat diseases of the lungs.
Pulmonary drug delivery (including both systemic and local) can itself be achieved by different approaches, including liquid nebulizers, metered dose inhalers (MDI""s) and dry powder dispersion devices. Dry powder dispersion devices are particularly promising for delivering protein and polypeptide drugs which may be readily formulated as dry powders. Many otherwise labile proteins and polypeptides may be stably stored as lyophilized or spray-dried powders by themselves or in combination with suitable powder carriers. The ability to deliver proteins and polypeptides as dry powders, however, is problematic in certain respects. The dosage of many protein and polypeptide drugs is often critical so it is necessary that any dry powder delivery system be able to accurately, and precisely (repeatedly) deliver the intended amount of drug. Moreover, many proteins and polypeptides are quite expensive, typically being many times more costly than conventional drugs on a per-dose basis. Thus, the ability to efficiently deliver the dry powders to the target region of the lung with a minimal loss of drug is critical. It is further desirable that powder agglomerates present in the dry powder be sufficiently broken up prior to inhalation by the patient to assure effective systemic absorption or other pulmonary delivery.
A particularly promising approach for the pulmonary delivery of dry powder drugs utilizes a hand-held device with a pump or other source of pressurized gas. A selected amount of the pressurized gas is abruptly released through a powder dispersion device, such as a Venturi tube, and the dispersed powder made available for patient inhalation. While advantageous in many respects, such hand-held devices are problematic in a number of other respects. The particles being delivered are very fine, usually being sized in the range from 1 xcexcm to 5 xcexcm, making powder handling and dispersion difficult. The problems are exacerbated by the relatively small volumes of pressurized gas, typically 2 ml to 25 ml at 20 to 150 psig, which are available in such devices. In particular, Venturi tube dispersion devices are unsuitable for difficult-to-disperse powders when only small volumes of pressurized gas are available. Moreover, Venturi tube dispersion devices have very small powder inlet orifices which are easily plugged by the powders used for pulmonary delivery. Another requirement for hand-held and other powder delivery devices is high dosage concentration. It is important that the concentration of drug in the bolus of gas be relatively high to reduce the number of breaths and/or volume of each breath required to achieve a total dosage. The ability to achieve both adequate dispersion and small dispersed volumes is a significant technical challenge.
It would therefore be desirable to provide methods and systems for the dispersion of dry powder protein, polypeptide, and other drugs which meet some or all of the above objectives.
2. Description of the Background Art
Dry powder dispersion devices for medicaments are described in a number of patent documents. U.S. Pat. Nos. 3,921,637 describes a manual pump with needles for piercing through a single capsule of powdered medicine. The use of multiple receptacle disks or strips of medication is described in EP 467172 (where a reciprocatable piercing mechanism is used to piercing mechanism through opposed surfaces of a blister pack); WO91/02558; WO93/09832; WO94/08522; U.S. Pat. Nos. 4,627,432; 4,811,731; 5,035,237; 5,048,514; 4,446,862; and 3,425,600. Other patents which show puncturing of single medication capsules include U.S. Pat. Nos. 4,338,931; 3,991,761; 4,249,526; 4,069,819; 4,995,385; 4,889,114; and 4,884,565; and EP 469814. WO90/07351 describes a hand-held pump device with a loose powder reservoir.
A dry powder sonic velocity disperser intended for industrial uses and very high flow rates is described in Witham and Gates, Dry Dispersion with Sonic Velocity Nozzles, presented at the Workshop on Dissemination Techniques for Smoke and Obscurants, Chemical Systems Laboratory, Aberdeen Proving Ground, Md., Mar. 14-16, 1983.
A pneumatic powder ejector having a suction stage and an injection stage is described in U.S. Pat. No. 4,807,814. The device comprises an axial gas Venturi tube and a lateral powder inlet.
Pittman and Mason (1986), Solids Handling Conference, Paper C4, pages C-41 to C-51, describes an ejector nozzle (FIG. 2) having an annular air inlet upstream of a venturi restriction.
SU 628930 (Abstract) describes a hand-held powder disperser having an axial air flow tube.
SU 1003926 (Abstract) describes a gas thermal coating injector.
Bubrik and Zhelonkina (1978), xe2x80x9cEjector Feeders for Pneumatic Transport Systems,xe2x80x9d in Chemical and Petroleum Engineering, Consultants Bureau, New York, describes differing efficiencies in several ejector designs.
Zholab and Koval (1979), Poroshkovaya Metallurgiya 6:13-16, describes effects of injector design on particle size.
Bohnet (1984) xe2x80x9cCalculation and Design of Gas/Solid-Injectors,xe2x80x9d in Powder Technology, pages 302-313, discusses conventional injector design.
Fox and Westawag (1988) Powder and Bulk Engineering, March 1988, pages 33-36, describes a venturi eductor having an axial air inlet tube upstream of a venturi restriction.
NL 7712041 (Abstract) discloses an ejector pump which creates suction and draws powder into a separator.
EP 347 779 describes a hand-held powder disperser having a collapsible expansion chamber.
EP 490 797 describes a hand-held powder disperser having a spring-loaded piston, where the piston carries a dispersion nozzle.
U.S. Pat. No. 3,994,421, describes a hand-held powder disperser having a collapsible deceleration chamber.
Pulmonary drug delivery is described in Byron and Patton (1994) J. Aerosol Med. 7:49-75.
The present invention provides methods and apparatus for efficient pulmonary delivery of accurate, precise, and repeatable dosages of powdered medicaments. The present invention will be particularly useful for the delivery of costly biopharmaceuticals such as protein, polypeptide and polynucleic acid drugs, but will also be useful for the systemic or localized delivery of any powdered medicament through the lungs. The delivery system and method produce substantially complete dispersion of the medicament powder with the break-up of any agglomerates of the powder which may have formed prior to delivery. The method and apparatus will find particular use in the dispersion of finely powdered medicaments from unit dosage receptacles, such as blister packs or cartridges, where the present invention is able to fluidize and extract substantially the entire amount of powder (usually at least 70% by weight, more usually at least 80%, and preferably at least 90%) within the receptacle, thus minimizing waste and enhancing the accuracy and precision of the dosage. The methods and approaches, however, will also find use with the dispersion and delivery of preselected metered amounts (boluses) of powdered medicaments from receptacles containing multiple dosage units, i.e. xe2x80x9cbulkxe2x80x9d powders contained in a single receptacle.
The methods and apparatus of the present invention are particularly suitable for the delivery of powders formed from discrete particles in the size range from 1 xcexcm to 5 xcexcm. Such powders, when properly dispersed in an aerosol, are optimum for delivery into the alveolar regions of the lung. However, they are particularly difficult to handle, and frequently become highly agglomerated during processing, packaging, and handling. Heretofore, handling characteristics of such powders have often been enhanced by combining the fine drug particles with larger carrier particles which have easier handling and dispersion characteristics. Use of a carrier, however, dilutes the drug, requiring a larger dispersion volume for a given drug dosage. The carrier particles can also cause choking when inhaled and serve no purpose other than improving handling characteristics. The present invention is able to achieve dispersion of fine drug particles with little or no carrier substances by a two-step dispersion method. The present invention, however, will be functional with drug compositions which include such carrier particles, as well as with diluents which may be necessary to achieve desired dosage concentrations.
The powders are first fluidized within the receptacle, as described above, resulting in fluidized particles and particle agglomerates which are then dispersed in the high velocity gas stream under conditions which break up such agglomerates. Such complete dispersion can be achieved with very low volumes of high velocity air and fluidization air, resulting in a well dispersed drug bolus having relatively high drug particle concentrations. Of course, the present invention is useful as well with drug formulations including a carrier diluent, or the like. The advantage of the present invention is that the use of carriers can often be reduced or eliminated altogether.
According to the method of the present invention, the powdered medicament is contained in a receptacle having a puncturable lid or other access surface. A powder inlet end of a feed tube is coupled with, i.e. engaged against or inserted through, a penetration in the access surface, and a high velocity airstream (usually sonic which provides sufficient shear forces to separate agglomerates into individual particles) is flowed past a portion of the tube, such as an outlet end, to draw powder from the receptacle, through the tube, and into the flowing airstream to form the desired aerosol. Usually, at least two spaced-apart discrete penetrations will be formed in the access surface prior to coupling the inlet end of the feed tube with one of the penetrations. The other penetration permits a separate stream of fluidization air to enter the receptacle, fluidize the powder, and sweep the receptacle of the fluidized powder to help assure that substantially all powder (preferably at least 70%, more preferably at least 80%, and still more preferably at least 90%) is removed into the flowing air stream. The high pressure gas stream will be generated by abruptly releasing a charge of pressurized gas through a flow path which intersects with the outlet end of the feed tube at an angle selected to both (1) induce sufficient fluidization air flow through the feed tube to fluidize and transport powder in the receptacle and (2) break up powder agglomerates which remain as the powder exits from the outlet end of the feed tube. The gas pressure prior to release will usually be at least about 15 psig (to achieve sonic velocity), preferably being at least 20 psig, and more preferably being in the range from 20 psig to 150 psig, and usually being in the range from 40 psig to 80 psig. The expanded volume of released gas (measured at standard temperature and pressure (STP) of 14.7 psig and 20xc2x0 C.) will thus usually be in the range from 2 ml to 25 ml, preferably being from 4 ml to 15 ml. Release of the high pressure gas can be effected by a manual trigger or optionally by sensing negative pressure resulting from the patient""s inspiration (i.e., can be breath-activated). As described in detail below, the high pressure gas stream will combine with the fluidization air stream at a volume ratio (measured at STP) in the range from 1:2 to 1:4 (high pressure gas:fluidization air) to produce the aerosol which is subsequently inhaled by the patient, optionally after capture in a plume capture chamber.
The method may further comprise the step of capturing the resulting discrete volume of aerosolized powder in a plume capture chamber prior to subsequent inhalation by the patient. The patient is then able to inhale the entire aerosolized dose from the chamber, concurrently with and/or followed by inhalation of ambient air which sweeps the capture chamber to further assure efficient delivery of the powder with minimum losses. Inhalation of chase air following the initial bolus of medication will drive the medication deep into the alveolar regions of the lung where absorption will occur. The method optionally further comprises advancing a plurality of powder-containing receptacles past the feed tube, typically in the form of a strip or disk, so the powder can be sequentially drawn and dispersed from each receptacle.
In another aspect of the method of the present invention, discrete quantities of a powdered medicament may be sequentially delivered from a receptacle or reservoir. In contrast with the previously described methods, the receptacle will include an amount of powdered medicament which is larger than that intended to be delivered in any single bolus, usually containing an amount which is sufficient for a large number of boluses, usually at least 5, preferably at least 10, and frequently 20 or more. The method comprises inserting the inlet end of the feed tube into the receptacle and flowing a high pressure gas stream past an outlet end of the feed tube to induce airflow from the receptacle through the tube. The powdered medicament is thus entrained in the airflow passing through the feed tube and combined with the high pressure gas stream at an outlet end of the feed tube. The high pressure gas stream can be repeatedly directed past the outlet end of the feed tube while the inlet end remains within the xe2x80x9cbulkxe2x80x9d powdered medicament receptacle.
Apparatus according to the present invention comprise a base enclosure having a support for the powder-containing receptacle at a fluidization location. The feed tube is mounted within the base enclosure and a mechanism for reciprocating the receptacle relative to the feed tube (or extending the feed tube relative to the receptacle) is optionally provided. A source of compressed gas for generating the high pressure gas is also provided, typically in the form of a hand-actuated pump, an electric (usually battery-operated) pump, a compressed gas container, a two-fluid system, or the like. The aerosolized powder dosage may thus be formed by reciprocating the receptacle relative to the feed tube so that the inlet end of the tube enters the receptacle. The high pressure gas stream is released while the tube is in or adjacent to the receptacle, and the resulting low pressure region at the outlet end of the feed tube draws fluidization air into the receptacle (preferably from the plume capture chamber which subsequently receives the aerosol, thus minimizing net air introduced from outside the device) to fluidize and extract the powder outward from the receptacle through the tube, and into the high velocity gas stream to form the desired dispersion. Usually, the capture chamber is disposed over and in-line with the outlet end of the feed tube to contain the xe2x80x9cplumexe2x80x9d of powder aerosol and allow the plume to quiesce prior to inhalation by the patient. The feed tube does not have jets or ejector tubes within the flow path, and the clear, undisrupted flow path reduces any tendency for the feed tube to clog or otherwise lose dispersion efficiency. Using air from the capture chamber as a source of fluidization gas is advantageous since it reduces the total volume of xe2x80x9cnewxe2x80x9d gas introduced to the chamber, making capture of the dispersion gas stream (i.e., the combination of the high pressure gas stream and the fluidization air stream) easier. Such recycling of air from the capture chamber, however, is not an essential feature of the present invention. Fluidization air can also be obtained directly from outside the device.
In a particular aspect of the apparatus of the present invention, the receptacle will be supported in a mechanism for advancing a continuous web (e.g. a strip or disk) which carries a plurality of receptacles past the fluidization location. Usually, the web advance mechanism includes a cartridge or carriage which holds the web and which is reciprocatably mounted relative to the feed tube so that the receptacles may be sequentially advanced while the cartridge and tube are separated, and the tube thereafter introduced into the receptacle by moving the cartridge and tube together. Optionally, the receptacle lid or other single access surface (i.e., a surface on one side of the receptacle) will be pierced immediately prior to introduction of the feed tube, usually using a separate piercing mechanism which pierces the lid as the cartridge is reciprocated relative to the feed tube. Alternatively, the access surface can be pierced simultaneously with the insertion of the feed tube. In the latter case, the inlet end of the feed tube will usually have a piercing structure and/or additional piercing structures will be provided to form additional penetrations for the entry of the fluidization air.
In a specific aspect of the apparatus of the present invention, the piercing mechanism will produce at least two spaced-apart holes in the lid, where one hole receives or engages the feed tube and the other hole(s) permit entry of displacement air to fluidize the powder and sweep the receptacle as powder is withdrawn through the feed tube. A conduit or other path may also be provided for directing air from the plume capture chamber back to the receptacle in order to at least partially provide the necessary displacement air. The hole for the feed tube may be formed simultaneously with or at a different time from the displacement air hole(s). For example, the displacement air hole(s) could be formed at a piercing station disposed ahead of the dispersion station with the feed tube hole formed at the dispersion station, or vice versa. It also may be desirable to provide a piercing mechanism at the dispersion station where the feed tube piercing structure is reciprocated relative to the receptacle in a separate motion from the displacement air hole piercing structure.
The present invention further provides apparatus for aerosolizing of powder comprising a feed tube having an inlet end, an outlet end, and a lumen defining an axial flow path between said inlet end and outlet end. At least one conduit is provided for flowing a high velocity gas stream past the outlet end in a direction which converges with the axial flow path at an angle in the range from 12.5xc2x0 to 65xc2x0. It has been found that the angle of convergence in this range induces a sufficient flow of fluidization air in the feed tube to efficiently empty an associated powder receptacle (typically removing and aerosolizing at least 80% and preferably at least 90% of the powder initially present in the receptacle) while also providing sufficient shear energy at the outlet end to substantially break up agglomerates which are present in the powder.
The aerosolizing apparatus may include two or more separate gas conduits which converge from different, usually opposite (diametrically opposed), sides of the flow path. Alternatively, the high pressure gas conduit may terminate in a single annular aperture which circumscribes the outlet end of the feed tube and which creates a gas flow path which converges on the axial flow path. The latter approach however, will generally be less preferred since it is difficult to manufacture annular apertures in the small size required. The total lumen area (A1) of the high pressure (dispersion) gas flow conduit(s) will usually be in the range from 0.05 mm2 to 0.3 mm2, while the throat of the feed tube immediately upstream of the gas conduit(s) tube will have a lumen area (A2) in the range from 0.5 mm2 to 10 mm2. The area (A3) and length of the mixing volume immediately downstream from the high velocity gas conduits are preferably in the range from the 0.6 mm2 to 11 mm2 and 0.5 mm to 3 mm, respectively. The feed tube upstream of the throat will usually have an area (A4) in the range from 0.6 mm2 to 15 mm2.
The aerosolizing apparatus may further include a diffuser tube extending from the outlet end of the mixing volume and having a lumen which is usually but not necessarily coaxially aligned with the feed tube lumen. The diameter of the diffuser tube lumen will increase in a direction away from the outlet end of the mixing volume, typically diverging at a half angle of 2xc2x0 to 10xc2x0 over a length in the range from 0.5 cm to 5 cm, usually having an outlet area which is about four times the inlet (mixing volume) area. The diffuser tube thus causes a reduction in the velocity of the gas stream exhausted from the outlet end of the mixing volume, where velocity is at a maximum, prior to entering the plume capture chamber. The plume continues to slow rapidly as it expands within the chamber and approaches a quiet or quiescent state prior to inhalation.
The present invention further provides a feed tube assembly comprising a casing, a flow-directing member, and a feed tube. The assembly is replaceable within the aerosol dispersion system, facilitating removal and cleaning or exchange of the assembly if it becomes plugged or fouled.
The invention provides an improved apparatus for aerosolizing a powdered medicament. The apparatus is of the type having a housing and a source of pressurized gas for aerosolizing the powder. Such an apparatus is improved by providing a pressurization cylinder, a piston slidable within the cylinder, and a release valve in communication with the cylinder. Further provided is a handle assembly having a handle operably attached to the piston and a means for closing the valve. In this manner, translation of the handle closes the valve and axially translates the piston within the cylinder to produce the pressurized gas.
In one aspect, the release valve comprises a valve stem connected to a valve poppet, and the means for closing the valve comprises a roller cam adjacent the valve stem for translating the valve stem to close the valve as the handle is translated radially outward from the housing. In another aspect, the handle assembly further includes a toggle link which moves over-center to hold the roller cam against the valve stem and keep the valve closed. In this way, the valve is held closed while the piston is translated back toward the housing to produce the pressurized gas. In a further aspect, the handle assembly includes a linkage between the handle and the piston. In this manner, the linkage reciprocally translates the piston between a retracted position and a charged position within the cylinder as the handle is translated radially outward and radially inward relative to the housing. With such a configuration, the handle may be moved radially outward to both close the valve and retract the piston, while inward movement of the handle charges the cylinder with pressurized gas.
In yet another aspect, an interlocking means is provided for preventing inward radial translation of the handle until the toggle link has moved over-center to hold the valve closed. Preferably, the interlocking means comprises a rack and a pawl. In a further aspect, a release button is provided for translating the roller cam from the over-center position to open the valve. In yet a further aspect, the cylinder preferably includes a one-way valve for allowing air to enter the cylinder as the piston is translated to the retracted position.
In one particular aspect, the powdered medicament is held within a receptacle. A feed tube is provided having an inlet end, an outlet end, and a lumen extending therebetween so that the inlet end may be inserted into the receptacle. In this way, compressed gas exiting the release valve may be flowed past the outlet end of the feed tube, with powder from the receptacle being extracted through the tube and dispersed in the flowing compressed gas to form the aerosol. Preferably, a means is provided for piercing at least one hole in an access surface of the receptacle simultaneously with inserting the inlet end of the feed tube into the receptacle. In a preferable aspect, the piercing means comprises a pair of pointed tabs, with the tabs being each disposed at an oblique angle relative to the access surface of the receptacle when the tabs are pierced through the access surface.
In another particular aspect, a means is provided for reciprocally translating the receptacle toward and away from the piercing means. The translating means preferably includes an over-center linkage for locking the receptacle in place upon insertion of the inlet end of the feed tube into the receptacle. In another aspect, a positioning pin is provided for aligning the receptacle in a preferred orientation relative to the piercing means while inserting the inlet end of the feed tube into the receptacle.
In yet another particular aspect, the handle assembly includes four linkages for attaching the handle to the housing. In this manner, the handle may be translated radially outward and radially inward relative to the housing with a generally constant force, and with a more linear motion than with a simple pivot. Further, such linkages reduce the distance that the handle must be translated away from the housing, thereby making easier hand operation of the handle assembly. In another aspect, a means is provided on or in association with the housing for producing verbal operating instructions.
The invention provides an exemplary apparatus for aerosolizing a powder held in a receptacle having a puncturable access surface. The apparatus includes a housing, a source of pressurized gas, a capture chamber attached to the housing, and a transjector assembly removably held within the housing. The transjector assembly includes a means for piercing the access surface of the receptacle and for receiving pressurized gas to draw powder from the receptacle and into the capture chamber. In a preferable aspect, the transjector assembly receives gas directly from the gas source and delivers powder directly to the capture chamber without powder passing through other portions of the apparatus.
In a particular aspect, an interface seal is provided between the transjector assembly and the housing so that pressurized gas may be passed from the housing to the transjector assembly without substantial loss of the gas. Preferably, the interface seal is angled relative to a central axis of the transjector assembly to facilitate easy removal of the transjector assembly from the housing. In another aspect, a receptacle seal is provided for forming a seal between the transjector and the receptacle. In a further aspect, the transjector assembly is keyed to be repeatedly received into the housing in a unique orientation.
In another particular aspect, the capture chamber is axially slidable over the housing so that the capture chamber may be placed in a collapsed position substantially covering the housing or an extended position forming an enclosure for receiving aerosolized powder. Preferably, at least one detent is provided in the housing and at least one notch is provided in the capture chamber, with the detent being received into the notch when the capture chamber is in the extended position. A spring is preferably provided for outwardly biasing the detent. In another aspect, the detent is generally V-shaped in geometry. In a further aspect, the capture chamber comprises an elongate chamber body having at least one elongate ridge or rib extending longitudinally along the body. The elongate ridge engages the housing when the chamber is collapsed to limit the amount of accumulated powder on the chamber that may be scraped from the chamber by the housing. In yet another aspect, the chamber body is asymmetrical in cross-sectional geometry and includes a mouthpiece. A cap is preferably removably held over the mouthpiece to prevent external dust and particulate from entering the chamber and to hold the powdered medicament within the chamber until ready to be inhaled. A seal is preferably provided between the cap and the mouthpiece, with the seal preferably being configured to function as a bleed valve to allow excess gas within the chamber to escape.
The invention further provides a receptacle for holding a powdered medicament, with the receptacle being adapted to be received into a housing of an aerosolizing apparatus. The receptacle includes a receptacle body having a puncturable access surface and a tab extending from the receptacle body. In this manner, the receptacle body may be received into an aperture in the housing with at least a portion of the tab remaining outside the housing. In one aspect, the tab includes a keyed hole adapted to receive an alignment pin in the aerosolizing apparatus. By keying the hole in the tab, the receptacle may be configured so that it may only be used with an apparatus having a mating alignment pin. In this way, the apparatus may be configured to receive only certain receptacles having a particular medicament.
The invention provides an improved method for aerosolizing a powdered medicament. The method is of the type wherein the powder is entrained and suspended in a flowing gas stream and comprises providing a housing having a pressurization cylinder, a piston slidable within the cylinder, a release valve in communication with the cylinder, and a handle for axially translating the piston and for closing the release valve. The handle is initially translated away from the housing to axially translate the piston within the cylinder to a retracted position and to close the release valve. The handle is then translated back toward the housing to translate the piston to a position where it creates a charge of pressurized gas. The valve is released following charging to abruptly discharge the pressurized gas.
In one particular aspect, translation of the handle in the direction of the housing is prevented until the release valve is closed. In this way, premature introduction of gas to the medicament is prevented until the cylinder is fully charged. In another aspect, the release valve is held closed while translating the handle back toward the housing so that gas in the cylinder may be charged by the piston. In a further aspect, the handle is kept generally parallel to the housing when translated. Preferably, the handle is translated toward the housing to pressurize the gas while applying a generally constant force to the handle.
In another particular aspect, the powder that is suspended in the released gas is introduced into a capture chamber while simultaneously bleeding off a preselected amount of gas from the capture chamber. In still another aspect, a transjector assembly is provided for receiving the pressurized gas and aerosolizing the powder. The transjector assembly is removably held in the housing so that it may periodically be removed from the housing for cleaning. In yet another aspect, verbal operating instructions are produced from the housing.
In still another particular aspect, a receptacle having a puncturable lid is provided for holding the medicament. The receptacle is translated toward the transjector assembly until the transjector assembly penetrates the lid. Preferably, the receptacle is guided toward the transjector so that the transjector penetrates the lid at a known and a predictable position. The receptacle is preferably held with the transjector assembly penetrating its lid until after the valve is released.
The invention provides an exemplary method for aerosolizing a powdered medicament. According to the method, receptacles are provided having a receptacle body and a tab extending from the receptacle body, with the powdered medicament being held within the receptacle bodies. One of the receptacles is inserted into a housing having an aperture, with the receptacle body being received within the aperture so that at least a portion of the tab remains outside the housing. The receptacle body is raised and simultaneously pierced and the powdered medicament in the receptacle is extracted in a gas stream that can be inhaled. The receptacle is lower, and the tab is then pulled to remove the receptacle from the housing.
In one aspect, the housing has a reciprocatable capture chamber for receiving the powder-bearing gas stream, and the chamber is preferably deployed prior to inserting the receptacle. Deploying of the chamber exposes the aperture, and insertion of the receptacle into the aperture prevents the chamber from retracting until the receptacle is removed.